Showing papers by "University of New Mexico published in 2000"
TL;DR: A theory is proposed that unites and organizes observations and generates many theoretical and empirical predictions that can be tested in future research by comparative biologists, archeologists, paleontologists, biological anthropologists, demographers, geneticists, and cultural anthropologists.
Abstract: Human life histories as compared to those of other primates and mammals have at least four distinctive characteristics: an exceptionally long life span an extended period of juvenile dependence support of reproduction by older post-reproductive individuals and male support of reproduction through the provisioning of females and their offspring. Another distinctive feature of our species is a large brain with its associated psychological attributes: increased capacities for learning cognition and insight. In this paper the authors propose a theory that unites and organizes these observations and generates many theoretical and empirical predictions. The authors present some tests of those predictions and outline new predictions that can be tested in future research by comparative biologists archaeologists paleontologists biological anthropologists demographers geneticists and cultural anthropologists. (authors)
1,702 citations
TL;DR: During human evolutionary history, there were “trade-offs” between expending time and energy on child-rearing and mating, so both men and women evolved conditional mating strategies guided by cues signaling the circumstances.
Abstract: During human evolutionary history, there were "trade-offs" between expending time and energy on child-rearing and mating, so both men and women evolved conditional mating strategies guided by cues signaling the circumstances. Many short-term matings might be successful for some men; others might try to find and keep a single mate, investing their effort in rearing her offspring. Recent evidence suggests that men with features signaling genetic benefits to offspring should be preferred by women as short-term mates, but there are trade-offs between a mate's genetic fitness and his willingness to help in child-rearing. It is these circumstances and the cues that signal them that underlie the variation in short- and long-term mating strategies between and within the sexes.
1,523 citations
TL;DR: The results suggest that the BIA equation provides valid estimates of SM mass in healthy adults varying in age and adiposity.
Abstract: The purpose of this study was to develop and cross-validate predictive equations for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis (BIA). Whole body SM mass, determine...
1,174 citations
TL;DR: In this article, the authors used high precision thermal ionization mass spectrometric (TIMS) methods to determine the half-life of zircons with concordant 238 U/ 238 U and 230 Th / 238 U atomic ratios.
1,171 citations
TL;DR: This study suggests that radical prostatectomy is associated with significant erectile dysfunction and some decline in urinary function, and these results may be particularly helpful to community-based physicians and their patients with prostate cancer who face difficult treatment decisions.
Abstract: ContextPatients with prostate cancer and their physicians need knowledge of
treatment options and their potential complications, but limited data on complications
are available in unselected population-based cohorts of patients.ObjectiveTo measure changes in urinary and sexual function in men who have undergone
radical prostatectomy for clinically localized prostate cancer.DesignThe Prostate Cancer Outcomes Study, a population-based longitudinal
cohort study with up to 24 months of follow-up.SettingPopulation-based cancer registries in 6 geographic regions of the United
States.ParticipantsA total of 1291 black, white, and Hispanic men aged 39 to 79 years who
were diagnosed as having primary prostate cancer between October 1, 1994,
and October 31, 1995, and who underwent radical prostatectomy within 6 months
of diagnosis for clinically localized disease.Main Outcome MeasuresDistribution of and change in urinary and sexual function measures reported
by patients at baseline and 6, 12, and 24 months after diagnosis.ResultsAt 18 or more months following radical prostatectomy, 8.4% of men were
incontinent and 59.9% were impotent. Among men who were potent before surgery,
the proportion of men reporting impotence at 18 or more months after surgery
varied according to whether the procedure was nerve sparing (65.6% of non–nerve-sparing,
58.6% of unilateral, and 56.0% of bilateral nerve–sparing). At 18 or
more months after surgery, 41.9% reported that their sexual performance was
a moderate-to-large problem. Both sexual and urinary function varied by age
(39.0% of men aged <60 years vs 15.3%-21.7% of older men were potent at ≥18
months [P<.001]; 13.8% of men aged 75-79 years
vs 0.7%-3.6% of younger men experienced the highest level of incontinence
at ≥18 months [P = .03]), and sexual function
also varied by race (38.4% of black men reported firm erections at ≥18
months vs 25.9% of Hispanic and 21.3% of white men; P
= .001).ConclusionsOur study suggests that radical prostatectomy is associated with significant
erectile dysfunction and some decline in urinary function. These results may
be particularly helpful to community-based physicians and their patients with
prostate cancer who face difficult treatment decisions.
1,146 citations
TL;DR: The redesigned MY09/11 primers were redesigned to increase the sensitivity of amplification across the type spectrum by using the same primer binding regions in the L1 open reading frame, and affords an increase in type-specific amplification sensitivity over that of the standard MY 09/11 primer system.
Abstract: Genital human papillomaviruses (HPVs) are commonly detected from clinical samples by consensus PCR methods. Two commonly used primer systems, the MY09-MY11 (MY09/11) primers and the GP5+-GP6+ (GP5+/6+) primers, amplify a broad spectrum of HPV genotypes, but with various levels of sensitivity among the HPV types. Analysis of the primer-target sequence homology for the MY09/11 primers showed an association between inefficient amplification of HPV types and the number and position of mismatches, despite accommodation of sequence variation by inclusion of degenerate base sites. The MY09/11 primers were redesigned to increase the sensitivity of amplification across the type spectrum by using the same primer binding regions in the L1 open reading frame. Sequence heterogeneity was accommodated by designing multiple primer sequences that were combined into an upstream pool of 5 oligonucleotides (PGMY11) and a downstream pool of 13 oligonucleotides (PGMY09), thereby avoiding use of degenerate bases that yield irreproducible primer syntheses. The performance of the PGMY09-PGMY11 (PGMY09/11) primer system relative to that of the standard MY09/11 system was evaluated with a set of 262 cervicovaginal lavage specimens. There was a 91.5% overall agreement between the two systems (kappa = 0.83; P < 0.001). The PGMY09/11 system appeared to be significantly more sensitive than the MY09/11 system, detecting an additional 20 HPV-positive specimens, for a prevalence of 62.8% versus a prevalence of 55.1% with the MY09/11 system (McNemar's chi(2) = 17.2; P < 0.001). The proportion of multiple infections detected increased with the PGMY09/11 system (40. 0 versus 33.8% of positive infections). HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and MM7 were detected at least 25% more often with the PGMY09/11 system. The PGMY09/11 primer system affords an increase in type-specific amplification sensitivity over that of the standard MY09/11 primer system. This new primer system will be useful in assessing the natural history of HPV infections, particularly when the analysis requires HPV typing.
1,128 citations
National Institutes of Health1, Indiana University – Purdue University Indianapolis2, George Washington University3, University of Cincinnati4, Emory University5, Case Western Reserve University6, University of Texas Southwestern Medical Center7, University of Miami8, Wayne State University9, University of Tennessee Health Science Center10, Stanford University11, University of New Mexico12, Yale University13
TL;DR: ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months' corrected age, and factors significantly associated with decreased morbidity included increased birth weight, female gender, higher maternal education, and white race.
Abstract: Objectives. The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401–1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. Study Design. A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months9 corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. Results. Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 ± 135 g, mean gestation (best obstetric dates) 26 ± 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index Conclusion. ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months9 corrected age.
1,117 citations
TL;DR: McGraw and Wong as mentioned in this paper described an appealing index of effect size, called CL, which measures the difference between two populations in terms of the probability that a score sampled at random from...
Abstract: McGraw and Wong (1992) described an appealing index of effect size, called CL, which measures the difference between two populations in terms of the probability that a score sampled at random from ...
1,104 citations
TL;DR: This paper showed that people use multiple approaches for solving the problem of retrieving an intention (prospective memory) after a delay, and that the extent to which prospective remembering is supported by relatively automatic processes and the probability with which prospective memory is likely to be successful when relying on automatic processes varies as a function of the characteristics of the prospective memory task, target cue, ongoing task, and individual.
Abstract: Prospective memory situations involve forming intentions and then realizing those intentions at some appropriate time in the future. An interesting feature of most prospective remembering is that recollection of the intended action occurs without an explicit request to attempt retrieval, and we present two views on how this type of remembering can be accomplished. One could strategically monitor the environment for the presence of the target event, or one could rely on anticipated environmental conditions more or less automatically reinstating the intended action. We present data supporting both views and argue that people use multiple approaches for solving the problem of retrieving an intention (prospective memory) after a delay. Moreover, we suggest that the extent to which prospective remembering is supported by relatively automatic processes (versus strategic resource-demanding monitoring) and the probability with which prospective memory is likely to be successful when relying on automatic processes varies as a function of the characteristics of the prospective memory task, target cue, ongoing task, and individual. We argue that the complexity of the empirical findings can best be understood by appealing to this multiprocess view of prospective memory. Copyright © 2000 John Wiley & Sons, Ltd.
1,021 citations
TL;DR: It is concluded that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting and bioengineering.
Abstract: Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.
1,010 citations
TL;DR: Analytical challenges inherent in the interpretation of focus group data are described and approaches for enhancing the rigor of analysis and the reliability and validity of focus groups findings are suggested.
Abstract: In the literature on focus groups, far more attention has been devoted to how groups are organized and conducted than to issues of analysis. Although exploitation of group dynamics is touted as a virtue of focus groups, there is very little guidance in the literature with respect to how differences between group and individual discourse impact the analysis and interpretation of focus group data. In this article, the authors describe analytical challenges inherent in the interpretation of focus group data and suggest approaches for enhancing the rigor of analysis and the reliability and validity of focus group findings.
TL;DR: In this paper, ARTIS is applied to computer security in the form of a network intrusion detection system called LISYS, which is shown to be effective at detecting intrusions, while maintaining low false positive rates.
Abstract: An artificial immune system (ARTIS) is described which incorporates many properties of natural immune systems, including diversity, distributed computation, error tolerance, dynamic learning and adaptation, and self-monitoring. ARTIS is a general framework for a distributed adaptive system and could, in principle, be applied to many domains. In this paper, ARTIS is applied to computer security in the form of a network intrusion detection system called LISYS. LISYS is described and shown to be effective at detecting intrusions, while maintaining low false positive rates. Finally, similarities and differences between ARTIS and Holland's classifier systems are discussed.
TL;DR: In most large hospitals in the United States CT scanning probably accounts for more than 10% of diagnostic radiology examinations and about two-thirds of the radiation dose, and most patients have multiple scan sequences.
Abstract: CT scanning is a relatively high-dose procedure. In spite of the use of magnetic resonance imaging, with faster CT scanners and helical techniques CT is becoming more common. There are few data from practice in the United States regarding the age and sex distribution of patients receiving CT scans, what type of scan and how many scans they receive, or how much radiation dose CT scans contribute. We reviewed over 33,700 consecutive CT examinations done at our institution in 1998 and 1999. Information on the types of scans as well as the age and sex distribution of the patients was determined. Between 1990 and 1999, CT examinations in our institution increased from 6.1% to 11.1% of all radiology procedures. Nineteen per cent of all patients seen in our department in the last year had at least one CT scan and more than half had multiple scans on the same day. Thirty-six per cent of all patients had a prior CT examination done on an earlier date. The male/female ratio of patients was 56/44. Studies of children age 0-15 years comprised 11.2% of scans. The highest percentage of scans was done in the 36-50-year-old age group. CT scanning accounted for 67% of the effective dose from diagnostic radiology. In most large hospitals in the United States CT scanning probably accounts for more than 10% of diagnostic radiology examinations and about two-thirds of the radiation dose. Most patients have multiple scan sequences. Studies done on children are probably more common than previously thought.
TL;DR: The results suggest that current screening practices in the United States are insufficient to detect a significant proportion of adenocarcinoma precursor lesions and the number of women at risk of cervical cancer has increased.
TL;DR: C-reactive protein (CRP) is an ancient highly conserved molecule and a member of the pentraxin family of proteins that is secreted by the liver in response to a variety of inflammatory cytokines.
Abstract: C-reactive protein (CRP) is an ancient highly conserved molecule and a member of the pentraxin family of proteins. CRP is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP increase very rapidly in response to trauma, inflammation, and infection and decrease just as rapidly with the resolution of the condition. Thus, the measurement of CRP is widely used to monitor various inflammatory states. CRP binds to damaged tissue, to nuclear antigens and to certain pathogenic organisms in a calcium-dependent manner. The function of CRP is felt to be related to its role in the innate immune system. Similar to immunoglobulin (Ig)G, it activates complement, binds to Fc receptors and acts as an opsonin for various pathogens. Interaction of CRP with Fc receptors leads to the generation of proinflammatory cytokines that enhance the inflammatory response. Unlike IgG, which specifically recognizes distinct antigenic epitopes, CRP recognizes altered self and foreign molecules based on pattern recognition. Thus, CRP is though to act as a surveillance molecule for altered self and certain pathogens. This recognition provides early defense and leads to a proinflammatory signal and activation of the humoural, adaptive immune system.
TL;DR: These pro?
Abstract: It is paradoxical that exotic species invade and displace native species that are well adapted to local environments. Yet, even those exotics that eventually become abundant and widespread, often do so only after having failed to establish following multiple earlier introductions. The first pattern, while not generally discussed in this context, is usually explained by exotic species pre-adaptations for human-altered environments and by a release from enemies. It can be understood further by examining the superior quality of colonists from large species-rich regions and the historical contingency of evolution. The second pattern is generally explained by invoking demographic and environmental stochasticity; how? ever, it can be understood further by examining the role of environmental variation over space and by metapopulation dynamics. These pro? cesses provide a context in which these patterns of invasion are not paradoxical, but instead, expected.
TL;DR: In this paper, the authors present a theory of endogenous protection by explicitly modeling government-industry interactions for which mere “black-box” models previously existed, and whether the Grossman-Helman model stands up to real-world data is investigated.
Abstract: Grossman and Helpman (1994) present a theory of endogenous protection by explicitly modeling government-industry interactions for which mere “black-box” models previously existed. They obtain a Ramsey pricing-type solution to the provision of protection which emphasizes the role of inverse import penetration ratios and import elasticities. On the lobbying side, the model makes predictions about lobbying competition and lobbying spending according to deadweight costs from protection. The model not only makes for richer theory in terms of rigor and elegance, but its predictions are directly testable. Whether the Grossman-Helman model stands up to real-world data is investigated in this paper. Predictions from both the protection side and lobbying side are tested using cross-sectional U.S. nontariff barrier data. We also compare the “second-generation” Grossman-Helpman model with a more traditional specification. Our results call for serious consideration of this model in the political economy literature.
Case Western Reserve University1, University of Texas Southwestern Medical Center2, National Institutes of Health3, University of Miami4, University of Tennessee Health Science Center5, Stanford University6, George Washington University7, Emory University8, Indiana University – Purdue University Indianapolis9, University of New Mexico10, Wayne State University11, University of Cincinnati12, Yale University13
TL;DR: Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN and Randomized trials are needed to evaluate the role of these common therapies.
Abstract: Objectives. In the era before widespread use of inhaled nitric oxide, to determine the prevalence of persistent pulmonary hypertension (PPHN) in a multicenter cohort, demographic descriptors of the population, treatments used, the outcomes of those treatments, and variation in practice among centers. Study Design. A total of 385 neonates who received ≥50% inspired oxygen and/or mechanical ventilation and had documented evidence of PPHN (2D echocardiogram or preductal or postductal oxygen difference) were tracked from admission at 12 Level III neonatal intensive care units. Demographics, treatments, and outcomes were documented. Results. The prevalence of PPHN was 1.9 per 1000 live births (based on 71 558 inborns) with a wide variation observed among centers (.43–6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal intensive care units at a mean of 12 hours of age (standard deviation: 19 hours). Wide variations in the use of all treatments studied were found at the centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, with a range of 27% to 93% of neonates. Other frequently used treatments included sedation (94%; range: 77%–100%), paralysis (73%; range: 33%–98%), and inotrope administration (84%; range: 46%–100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%–81%) of neonates. Despite the wide variation in practice, there was no significant difference in mortality among centers. Mortality was 11% (range: 4%–33%). No specific therapy was clearly associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with hyperventilation were compared with those treated with alkali infusion. Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. Conclusions. Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.
TL;DR: Remarkably, Rab5 GTPase links budding, cytoskeletal transport and docking/fusion activities, which may provide an integrated system for the general coordination of endocytic pathways to maintain organelle homeostasis.
Abstract: Endocytosis is characterized by vesicular transport along numerous pathways. Common steps in each pathway include membrane budding to form vesicles, transport to a particular destination, and ultimately docking and fusion with the target membrane. Specificity of vesicle targeting is rendered in part by associated Rab GTPases. This review summarizes current knowledge about Rab GTPase functions in the endocytic pathways and provides insight into the regulation of Rab GTPase activity and mechanisms of Rab protein function. Functional assays have identified some Rab proteins that operate on individual pathways, but Rab proteins in several pathways remain controversial or have not been identified. Control of Rab GTPase activity is exerted through multiple levels of regulation. Significant new information pertaining to Rab protein function in regulating transport has emerged. Remarkably, Rab5 GTPase links budding, cytoskeletal transport and docking/fusion activities. This paradigm will most likely be generally applicable to other Rab GTPase pathways. Together with the cross-talk between different Rab proteins and their effectors, this may provide an integrated system for the general coordination of endocytic pathways to maintain organelle homeostasis.
TL;DR: It is shown that PMN isolated from the site of infection contain viable intracellular organisms and that these infected PMN are sufficient to establish infection in a naive animal and that modulation of the inflammatory response is sufficient to significantly alter morbidity and mortality induced by S. aureus infection.
Abstract: Neutrophils have long been regarded as essential for host defense against Staphylococcus aureus infection. However, survival of the pathogen inside various cells, including phagocytes, has been proposed as a mechanism for persistence of this microorganism in certain infections. Therefore, we investigated whether survival of the pathogen inside polymorphonuclear neutrophils (PMN) contributes to the pathogenesis of S. aureus infection. Our data demonstrate that PMN isolated from the site of infection contain viable intracellular organisms and that these infected PMN are sufficient to establish infection in a naive animal. In addition, we show that limiting, but not ablating, PMN migration into the site of infection enhances host defense and that repletion of PMN, as well as promoting PMN influx by CXC chemokine administration, leads to decreased survival of the mice and an increased bacterial burden. Moreover, a global regulator mutant of S. aureus (sar-) that lacks the expression of several virulence factors is less able to survive and/or avoid clearance in the presence of PMN. These data suggest that the ability of S. aureus to exploit the inflammatory response of the host by surviving inside PMN is a virulence mechanism for this pathogen and that modulation of the inflammatory response is sufficient to significantly alter morbidity and mortality induced by S. aureus infection.
TL;DR: In this paper, a new class of poly(bridgedsilsesquioxane) mesophases BSQMs with integral organic functionality has been reported, where the organic constituents are incorporated into the framework as molecularly dispersed bridging ligands.
Abstract: Since the discovery of surfactant-templated silica mesophases, the development of organic modification schemes to impart functionality to the pore surfaces has received much attention. Most recently, using the general class of compounds referred to as bridged silsesquioxanes (RO){sub 3}Si-R{prime}-Si(OR){sub 3} (Scheme 1), three research groups have reported the formation of a new class of poly(bridgedsilsesquioxane) mesophases BSQMs with integral organic functionality. In contrast to previous hybrid mesophases where organic ligands or molecules are situated on pore surfaces, this class of materials necessarily incorporates the organic constituents into the framework as molecularly dispersed bridging ligands. Although it is anticipated that this new mesostructural organization should result in synergistic properties derived from the molecular scale mixing of the inorganic and organic components, few properties of BSQMs have been measured. In addition samples prepared to date have been in the form of granular precipitates, precluding their use in applications like membranes, fluidics, and low k dielectric films needed for all foreseeable future generations of microelectronics.
TL;DR: It is suggested that sarcopenia is a progressive process, particularly in elderly men, and occurs even in healthy independently living older adults who may not manifest weight loss.
Abstract: Skeletal muscle loss or sarcopenia in aging has been suggested in cross-sectional studies but has not been shown in elderly subjects using appropriate measurement techniques combined with a longitu...
TL;DR: Many ecophysiological traits—considered here as all aspects of resource uptake and utilization, including biochemistry, metabolism, gas exchange, leaf structure and function, nutrient and biomass allocation, canopy structure, and growth—are likely to influence fitness and undergo adaptive evolution.
Abstract: functional diversity, which underlies variation in growth rates, productivity, population and community dynamics, and ecosystem function. The broad congruence of these variations with climatic and environmental conditions on local, regional, and global scales has fostered the concept that plant ecophysiological characteristics are well adapted to their local circumstances. For example, the repeated occurrence of plants with CAM (Crassulacean Acid Metabolism) photosynthesis and succulent leaves or stems in severely water-limited environments, and the independent evolution of these traits in numerous plant lineages, provides compelling evidence of the physiological evolution of these water-conserving traits under the influence of natural selection (Ehleringer and Monson 1993). Similarly, studies of the evolution of heavy metal tolerance confirm that natural selection may cause rapid ecophysiological evolution in just a few generations, leading to local adaptation in populations just a few meters apart (Antonovics et al. 1971). Many ecophysiological traits—considered here as all aspects of resource uptake and utilization, including biochemistry, metabolism, gas exchange, leaf structure and function, nutrient and biomass allocation, canopy structure, and growth—are likely to influence fitness and undergo adaptive evolution. Traits affecting the assimilation and use of resources such as carbon, water, and nutrients directly influence plant growth. Patterns of resource allocation to growth, reproduction, defense, and stress tolerance are also likely to be under strong selection. Phenotypic plasticity, the expression of different phenotypes by
TL;DR: Estimates of the mechanical and entropic work done by the enzyme show that T7 DNA polymerase organizes two template bases in the polymerization site during each catalytic cycle, and finds a force-induced 100-fold increase in exonucleolysis above 40 pN.
Abstract: T7 DNA polymerase1,2 catalyses DNA replication in vitro at rates of more than 100 bases per second and has a 3′→5′ exonuclease (nucleotide removing) activity at a separate active site. This enzyme possesses a ‘right hand’ shape which is common to most polymerases with fingers, palm and thumb domains3,4. The rate-limiting step for replication is thought to involve a conformational change between an ‘open fingers’ state in which the active site samples nucleotides, and a ‘closed’ state in which nucleotide incorporation occurs3,5. DNA polymerase must function as a molecular motor converting chemical energy into mechanical force as it moves over the template. Here we show, using a single-molecule assay based on the differential elasticity of single-stranded and double-stranded DNA, that mechanical force is generated during the rate-limiting step and that the motor can work against a maximum template tension of ∼34 pN. Estimates of the mechanical and entropic work done by the enzyme show that T7 DNA polymerase organizes two template bases in the polymerization site during each catalytic cycle. We also find a force-induced 100-fold increase in exonucleolysis above 40 pN.
TL;DR: In this article, the authors investigated 6 of the 19 spin-offs from the 55 research centers at the University of New Mexico (UNM) in 1997 and identified two types of spin-off: (1) planned, when the new venture results from an organized effort by the parent organization, and (2) spontaneously occurring, when a new company is established by an entrepreneur who identifies a market opportunity and who founds the spinoff with little encouragement (and perhaps with discouragement) from the parent organisation.
TL;DR: Stroke patients with ideomotor limb apraxia who had damage lateralized to a left hemispheric network involving the middle frontal gyrus and intraparietal sulcus region revealed that discrete areas in the left hemisphere of humans are critical for control of complex goal-directed movements.
Abstract: The frontal and parietal cortex are intimately involved in the representation of goal-directed movements, but the crucial neuroanatomical sites are not well established in humans. In order to identify these sites more precisely, we studied stroke patients who had the classic syndrome of ideomotor limb apraxia, which disrupts goal-directed movements, such as writing or brushing teeth. Patients with and without limb apraxia were identified by assessing errors imitating gestures and specifying a cut-off for apraxia relative to a normal control group. We then used MRI or CT for lesion localization and compared areas of overlap in those patients with and without limb apraxia. Patients with ideomotor limb apraxia had damage lateralized to a left hemispheric network involving the middle frontal gyrus and intraparietal sulcus region. Thus, the results revealed that discrete areas in the left hemisphere of humans are critical for control of complex goal-directed movements.
TL;DR: It is demonstrated that interactions among unrelated genes are the major cause of robustness against mutations, which is probably an evolved response of genetic networks to stabilizing selection.
Abstract: There are two principal mechanisms that are responsible for the ability of an organism's physiological and developmental processes to compensate for mutations. In the first, genes have overlapping functions, and loss-of-function mutations in one gene will have little phenotypic effect if there are one or more additional genes with similar functions. The second mechanism has its origin in interactions between genes with unrelated functions, and has been documented in metabolic and regulatory gene networks. Here I analyse, on a genome-wide scale, which of these mechanisms of robustness against mutations is more prevalent. I used functional genomics data from the yeast Saccharomyces cerevisiae to test hypotheses related to the following: if gene duplications are mostly responsible for robustness, then a correlation is expected between the similarity of two duplicated genes and the effect of mutations in one of these genes. My results demonstrate that interactions among unrelated genes are the major cause of robustness against mutations. This type of robustness is probably an evolved response of genetic networks to stabilizing selection.
TL;DR: A geographic information system (GIS) was used to measure actual patient travel distances to radiationtreatment facilities to more precisely examine the relationship between travel distance and receipt of radiotherapy after BCS.
Abstract: Breast-conserving surgery (BCS) followed by radiation therapy is an efficacious alternative treatment to mastectomy for women with early-stage breast cancer(1,2).However, 15%–30% of the women treated with BCS for early-stage disease fail to undergo postoperative breast irradiation, despite the known increased risk of ipsilateral recurrence associated with the omission of radiotherapy (3–8). Older age has been identified as a major determinant of not receiving radiotherapy after BCS (4,6,7,9). Other factors that could account for failure to receive radiation therapy, particularly among younger women, remain to be identified. Travel distance to a radiationtreatment facility may influence the receipt of postoperative breast irradiation. Radiotherapy that follows BCS typically involves daily treatments (weekends excluded), for a period of 5–6 consecutive weeks. The necessity of long-distance travel may increase the inconvenience or cost of radiotherapy to a point where it simply is not feasible to receive treatment. A study of breast cancer treatment conducted in the midto late-1980s in the Seattle–Puget Sound area found that living in a county without a radiationtreatment facility was associated with a 50% lower likelihood of receiving radiotherapy after BCS(4). A similar contemporaneous study in New Mexico (3) found no relationship between radiotherapy and travel distance, but the analysis was limited to manual identification of geographic clustering of BCS patients not receiving radiotherapy. In this study, we used a geographic information system (GIS) to measure actual patient travel distances to radiationtreatment facilities to more precisely examine the relationship between travel distance and receipt of radiotherapy after BCS. For our analysis, all cases of localized breast cancer diagnosed in 1994 and 1995 in female residents of New Mexico were selected from the New Mexico Tumor Registry (NMTR) database. The NMTR, a member of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, 1 collects information on all cases of cancer in New Mexico residents by use of the methods previously described(3,8). Native-American women were excluded from the analysis because the NMTR does not record their addresses at diagnosis. Stage of cancer at diagnosis was coded according to the SEER Summary Staging Guide (10), which defines localized cancer as an invasive cancer confined to the organ of origin. For classification of patients by treatment received, we considered all therapy that occurred in the first 4 months of cancer-directed therapy, the standard SEER definition for the first course of therapy. Surgery was classified as either mastectomy or BCS. BCS included lumpectomy or excisional biopsy, quadrantectomy, wedge resection, partial mastectomy, and subcutaneous mastectomy. For the BCS case subjects, we considered that adjuvant radiotherapy was received if the NMTR record documented radiotherapy during the first course of therapy. The address at diagnosis was obtained for each case subject from the NMTR database and geocoded by use of ArcView 3.0a software (Environmental Systems Research Institute, Redlands, CA). Approximately 70% of the case subjects were geocoded to a unique street address. The remaining 30% of the subjects, most of whom had either post office boxes or rural routes as their addresses, were geocoded to the centroids of their ZIP codes. Twelve radiation-treatment facilities were operational in New Mexico or in nearby areas in 1995. Four facilities were located in Albuquerque, NM; two in Las Cruces, NM; one each in Santa Fe, NM, Roswell, NM, Farmington, NM, and Carlsbad, NM; and one each in El Paso, TX, and Durango, CO. Each treatment facility was geocoded to a unique street address. We assumed that each patient was treated at the nearest facility and used the GIS to calculate the shortest travel distance to it. A total of 1122 women diagnosed with localized breast cancer were included in the analysis. Of these, 533 (48%) were treated with BCS, and 409 (77%) received radiation therapy following BCS (Table 1). Age was a strong and statistically significant predictor of post-BCS radiotherapy (two-sided P for trend <.0001). Among women less than 60 years of age, 83% received follow-up breast irradiation compared with 79% of those aged 60–69 years and 63% of those 70 years and older. After adjusting for the effects of race/ethnicity and travel distance, patients 70 years and older were roughly three times less likely to receive radiotherapy after BCS compared with patients younger than 60 years. Race/ethnicity was not predictive for receipt of radiotherapy following BCS. After adjustment for age, the likelihood of receiving radiotherapy following BCS decreased significantly with increasing travel distance to the nearest
TL;DR: This work combines silica–surfactant self-assembly with three rapid printing procedures—pen lithography, ink-jet printing, and dip-coating of patterned self-assembled monolayers—to form functional, hierarchically organized structures in seconds.
Abstract: Living systems exhibit form and function on multiple length scales and at multiple locations. In order to mimic such natural structures, it is necessary to develop efficient strategies for assembling hierarchical materials. Conventional photolithography, although ubiquitous in the fabrication of microelectronics and microelectromechanical systems, is impractical for defining feature sizes below 0.1 micrometres and poorly suited to pattern chemical functionality. Recently, so-called ‘soft’ lithographic approaches1 have been combined with surfactant2,3 and particulate4 templating procedures to create materials with multiple levels of structural order. But the materials thus formed have been limited primarily to oxides with no specific functionality, and the associated processing times have ranged from hours to days. Here, using a self-assembling ‘ink’, we combine silica–surfactant self-assembly with three rapid printing procedures—pen lithography, ink-jet printing, and dip-coating of patterned self-assembled monolayers—to form functional, hierarchically organized structures in seconds. The rapid-prototyping procedures we describe are simple, employ readily available equipment, and provide a link between computer-aided design and self-assembled nanostructures. We expect that the ability to form arbitrary functional designs on arbitrary surfaces will be of practical importance for directly writing sensor arrays and fluidic or photonic systems.